Absorbable intravascular devices that shorten upon expansion creating space for vascular movement

ABSTRACT

A multi-element, vascular stent may be used to maintain or enhance patency of a blood vessel. The stent may be used in peripheral blood vessels, which may be long and/or tortuous. By using multiple, separate stent elements that are balloon expandable, the multi-element stent may be stronger than a traditional self-expanding stent but may also be more flexible, due to its multiple-element configuration, than a traditional balloon-expandable stent. Individual stent elements shorten upon expansion creating a space between stent elements. The distance between stent elements when deployed may be based on characteristics of the stent and the target vessel location such that the stent elements do not touch one another during skeletal movement. Thus, the multi-element, vascular stent described herein may be particularly advantageous for treating long lesions in tortuous peripheral blood vessels

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/972,976 filed on Dec. 7, 2020 which is a 35 U.S.C. § 371_nationalphase filing of PCT patent application no. PCT/US19/35861 filed on Jun.6, 2019 which claims priority to U.S. provisional patent application No.62/682,727 entitled ABSORBABLE INTRAVASCULAR DEVICES THAT SHORTEN UPONEXPANSION CREATING SPACE FOR VASCULAR MOVEMENT filed on Jun. 8, 2018.

FIELD OF THE INVENTION

The present application pertains generally to the field of medicaldevices. More specifically, the present application pertains to thedesign and manufacture of intravascular stents intended to maintainpatency (blood flow) of blood vessels (arteries and veins).

BACKGROUND

Atherosclerotic cardiovascular disease or “hardening of the arteries” isthe leading cause of death and disability in the world accounting fornearly one-third of all human mortality. Although some developed nationshave made significant strides in modifying risk factors and changinglifestyle behaviors, the global prevalence of atherosclerotic disease isstill rising with some projections predicting >23 million annual deathsby the year 2030. The economic burden is staggering; in the UnitedStates alone, the estimated yearly cost treating atherosclerosis and itssequelae exceeds $200 billion.

Atherosclerosis is a process of pathological arterial aging. In youth,supple elastin fibers within the arterial media provide the structuralelasticity and compliance required for arterial pulsation and pulse wavetransmission. Over decades, however, the persistent pressure and motionslowly denatures structural matrix proteins causing elastin fatigue andfracture. The result is a slow but inexorable loss of distensibility;the arterial wall chronically stiffens. With the loss of pulsatility andwave reflection, the flow velocity profile becomes blunted; flowreversal is lost and the modulus of antegrade flow is attenuated. Thiscreates long periods of relative stasis in diastole and increasingparticle and cellular residence time at the wall. The dysfunctional wallbeneath the stagnant boundary layer begins to accumulate circulatingatherogenic cholesteryl fatty acyl esters and triglycerides particles,particularly apolipoprotein B-containing lipoproteins. Oxidativemodification of the lipoproteins activates the overlying endothelium tosecrete chemokines which attract blood-borne monocytes rolling along theendothelium to tether to the vascular surface made sticky by exposure ofadhesion molecules and tissue factor. Diapedesis of firmly attachedmonocytes traps the cells within the thickened subendothelial space.Thus initiated, the ongoing pathological process generates fatty,occlusive lesions via cholesterol-loaded foam cells, continuedrecruitment and infiltration of inflammatory and hematopoietic cells,and a progressive accumulation of lipid matrix and smooth muscleproliferation that slowly begins to raise the endothelium and encroachupon the arterial lumen. When grown large enough to reduce the flow ofblood and oxygen to vital organs, atherosclerotic plaques produce thechronic clinical syndromes of chest pain (angina pectoris), mini-stroke(transient ischemic attack) and poor circulation (claudication). Morecomplex plaques with ossified cores and degenerating fibrous caps canabruptly rupture leading to acute occlusion of the arteries in whichthey reside. These generate the critical, life-threatening clinicalevents of heart attack (myocardial infarction), stroke (cerebrovascularaccident) and gangrene (critical limb ischemia).

The first stent type to be widely applied to the treatment ofatherosclerotic plaques was a balloon-expandable stents (BES) designedas an open mesh tube comprised of stainless steel. When crimped onto anangioplasty balloon it could be advanced through the arterial treecoaxially and deployed directly within the plaque. Stent implantationcreated a larger and more durable flow channel as compared to balloonangioplasty alone.

In the modern era, balloon-expandable stents are deployed in virtuallyevery case of percutaneous coronary intervention (PCI) and in about halfof all peripheral interventional procedures.

In order to prop open large arteries and avoid excessive recoil anddeformation, peripheral BES are rigid medical devices. They aretypically designed to withstand pressures of 0.5-2×10⁵ Pa (375-1500mmHg, 0.05-0.2 N/mm²), non-physiologic forces that far exceed any intra-or extravascular pressure observed within the human body. In fact, BESare more than ten times rigid than the vessels they occupy. Because theyare so rigid, BES can only be implanted in a limited number of anatomiclocations, namely those with minimal or highly predictable arterialmotion such as the coronary, renal and common iliac arteries. As such,implantation of BES are absolutely contraindicated in a number ofimportant peripheral vascular beds including the carotid, subclavian,external iliac, common femoral, superficial femoral and poplitealarteries.

The rigidity of BES also severely limits their usable length. Implantedstents that are too long will kink or tear arteries in motion leading torestenosis, thrombosis, pseudoaneurysm formation and, in some cases,device fracture and migration. Knowing their dangers, stentmanufacturers make their devices available in limited lengths. Althoughatherosclerotic lesions in peripheral arteries can be several hundred mmlong, the longest available BES is only 60 mm. They are clearlyinadequate for intervention in the leg where lesions >200 mm areroutinely encountered.

As early as 1969, it was theorized that intravascular stents should beflexible rather than rigid. First developed for aerospace applications,an equiatomic alloy made of nickel-titanium called nitinol was thoughtto exemplify the ideal mechanical properties for the scaffolding ofblood vessels. One property was superelasticity, or the ability of ametal to return to its original shape after a substantial deformation.This assured flexibility within arteries in motion within the humanbody. The other property was shape memory, or the ability of an alloy tobe annealed at one temperature, substantially deformed at a lowertemperature, then returned to its original shape when heated. Thisallowed nitinol stents to be compressed into their delivery systems atlow temperatures, then released and expanded within the warm mammalianenvironment at the time of implantation.

The first self-expanding nitinol stent (SES) to be approved for clinicaluse was a simple, coiled wire made of nitinol. It was introduced intothe American market in 1992. Seamless tubes of nitinol became availableshortly thereafter, enabling the development of laser-cut, tubularnitinol stents. In the modern era, tubular, nitinol SES are the mostcommon devices deployed in long, flexible blood vessels such as theexternal iliac and superficial femoral arteries.

Because SES generate much less force than BES, they expand vessels muchless completely. In order to get them to expand more fully, SES areroutinely post-dilated with high-diameter balloons following theirdeployment. Even after repeated balloon dilatation, however, therelatively weak SES cannot overcome the inward force of the recoilingartery resulting in an insufficient post-procedure diameter. This is asurprisingly frequent occurrence after SES deployment, especially inperipheral arteries burdened with significant atherosclerosis disease.In one study, underexpansion of the target lesion (>30% residualstenosis) was observed in 70% of cases after SES implantation intocalcific arteries.

The second drawback of the use of nitinol SES is their disquietingtendency toward fracture. Only occasionally observed with BES, SESfracture is alarmingly common, as high as 65% in one clinical report.Although not fully understood, one attractive hypothesis for thisphenomenon is that fracture may be a function of the uniquebiomechanical forces exerted on stents dwelling in the lowerextremities. Movement of the legs is a complex motion; loading of thehips and knees during ambulation repeatedly compresses the arteriesaxially and can even produce multidimensional bends, twists and kinks.The result is single or multiple strut fractures or, in severe cases,complete stent transection. Fracture is more common after implantationof long and/or overlapping stents and, possibly, in more activepatients. Fracture of intravascular stents is clearly associated withrestenosis, although it remains controversial whether the relationshipis associative or causal.

The unique mechanism and design of SES assures that the pattern ofchronic forces exerted upon the stented artery are far different thanfor BES. After deployment of BES, the forces exerted upon the artery arestatic and temporary. The artery is perturbed by the initial stretch andstent deployment but, once recovered, heals completely and returns toquiescence. Vessels that house a nitinol SES, however, are continuallysubjected to the chronic outward forces (COF) exerted by theever-expanding and twisting device. A COF accompanies all SESimplantations because, by definition, SES must be “oversized” whenimplanted. That is to say that the nominal diameter of the stent must,in all cases, exceed the target lesion's reference vessel diameter (RVD)so that the flexible and non-anchored device will remain in placefollowing deployment. Because the final diameter of the device is alwaysless than its nominal “shape memory” diameter when manufactured, it willcontinue to exert an outward expansive force upon the wall of the vesseluntil such time that its nominal diameter is reached (if ever). Combinedwith the motion of the vessels in which SES are typically implanted,this assures a continual and chronic perturbation of the vessel wall formany years following device deployment. The artery responds with chronicinflammation, foreign body reaction, smooth muscle cell proliferationand restenosis. This is particularly troublesome in anatomic areas proneto bending and twisting, such as the common femoral artery. The problemis so prevalent that implantation of nitinol SES at the hip or knee issurgically contraindicated.

Lastly, although nitinol SES are far more flexible than their BEScounterparts, continued thickening of arteries treated with SES assuresthat the stented artery will eventually be rendered more rigid. Evenarteries treated with so-called “flexible” stents will generate asignificant foreign body response, stiffen, and induce kinking andtwisting of the unstented segments. Exaggerated movement of theremaining artery may still allow limited movement and preserve patency,but the resultant aberrant flow patterns and conformations too oftenlead to thrombosis and failure.

Given the non-physiologic nature of SES in the high-resistanceperipheral vasculature, their poor overall effectiveness is notsurprising. The one-year primary patency of superficial femoral arteriestreated with SES remains a dismal 60% and continues to decline with eachsuccessive year.

To address the myriad problems associated with permanent metal implants,stents that slowly dissolve after deployment have long been imagined.So-called “bioresorbable vascular scaffolds” (BVS) potentially offerseveral key biologic and physiologic advantages including, (1) effectivescaffolding without the permanence of a metal implant, (2) attenuationof inflammation and chronic foreign body reaction leading to reducedrestenosis and enhanced long-term patency, (3) assistance of adaptivevascular remodeling, (4) restoration of physiologic vasoactive function,and (5) facilitation of imaging and surveillance during follow-up.

The original bioresorbable device was the “catgut” surgical suture,first evident in the historical record some four millennia ago. Catgutsutures are derived from dried sheep, goat or bovine intestine, but haveretained the name “catgut” probably because they were also used asstrings for musical instruments sometimes referred to as “kits”. Catgutsutures are enzymatically degraded and resorbed in vivo so can beclassified as bioresorbable. More contemporary bioresorbable surgicalsutures are synthetic. Other, more recently developed bioresorbablemedical devices includes bioresorbable screws and fracture plates forthe treatment of traumatic injuries, indwelling scaffolds that serve asa basis for tissue engineering and regenerative medicine,chemotherapy-loaded polymers for therapeutic oncology, inert syntheticwraps for the prevention of post-operative peritoneal adhesions,bioabsorbable scaffolds for stenting of the upper airways and Eustachiantubes, and bioresorbable intravascular scaffolds (stents).Unfortunately, recent, more longer-term results have raised questionsregarding the safety and efficacy of the first-generation absorbablecoronary stent.

Therefore, it would be advantageous to have a stent for use invasculature that is rigid upon implantation so as to maximally dilateand scaffold the artery, but then slowly decreases in rigidity to allowthe blood vessel to return to its original, healthy, flexible state. Atleast some of these objectives will be met by the embodiments describedbelow.

SUMMARY

The embodiments herein describe a device for placement within a bloodvessel to maintain or enhance blood flow through the blood vessel. Thedevice may comprise multiple, balloon-expandable, bioresorbable,vascular stent elements configured to be implanted in the blood vesselas a multi-element stent. The stent elements may be positioned seriallyalong a longitudinal length of a balloon with a space between the stentelements in an unexpanded state of 1 mm or less. The stent elements maybe configured to shorten upon balloon expansion to an expanded state ata target vessel location to create a space between the stent elements inthe expanded state such that the stent elements do not touch one anotherat the target vessel location during skeletal movement. The stent isconfigured to be radially rigid and longitudinally flexible afterimplantation at the target vessel location.

Cell patterns of the stent elements may be configured to shorten thestent elements upon expansion and provide the space between the stentelements in the expanded state. In an embodiment stent elements compriseone or more shortening sections configured to shorten upon expansion tothe expanded state and one or more lengthening sections configured tolengthen upon expansion to the expanded state. The shortening sectionmay comprise closed cells. Additionally or alternatively, shorteningsections may comprise open cells with one or more struts connecting oneor more peaks of a first ring to one or more peaks of a second ring. Thelengthening section may comprise open cells with one or more strutsconnecting one or more valleys of a first ring to one or more valleys ofa second ring.

In some embodiments, the stent may be formed from a material comprisingpoly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), poly(D,L-lacticacid) (PDLLA), semi crystalline polylactide, polyglycolic acid (PGA),poly(lactic-co-glycolic acid) (PLGA), poly(iodinated desaminotyrosyl-tyrosine ethyl ester) carbonate, polycaprolactone (PCL),salicylate based polymer, polydioxanone (PDS), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride,poly(glycolic acid-co-trimethylene carbonate), poly(iodinateddesaminotyrosyl-tyrosine ethyl ester) carbonate, polyphosphoester,polyphosphoester urethane, poly(amino acids), cyanoacrylates,poly(trimethylene carbonate), poly(iminocarbonate), polyalkyleneoxalates, polyphosphazenes, polyiminocarbonates, and aliphaticpolycarbonates, fibrin, fibrinogen, cellulose, starch, collagen,polyurethane including polycarbonate urethanes, polyethylene,polyethylene terephthalate, ethylene vinyl acetate, ethylene vinylalcohol, silicone including polysiloxanes and substituted polysiloxanes,polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG,PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinyl pyrrolidone,polyacrylamide, or combinations thereof.

In an embodiment, the stent comprises a therapeutic drug. Thetherapeutic drug may prevent or attenuate inflammation, celldysfunction, cell activation, cell proliferation, neointimal formation,thickening, late atherosclerotic change or thrombosis.

In an embodiment, the radial rigidity of the stent is slowly attenuatedas its structural polymer is unlinked and metabolized such that thestent slowly becomes more flexible causing adaptation and remodeling ofthe vessel and restoration of the vessel's elasticity.

A method for manufacturing an intravascular stent may comprise loading amulti-element stent comprising multiple individual stent elements ontoan inflatable balloon in an expanded state such that the stent elementsare positioned serially along a longitudinal length of the balloon andthe stent elements do not touch one another. The stent elements may bespaced such that the stent elements do not touch one another at a targetvessel location during skeletal movement. The balloon may be deflatedand the multi-element crimped to an unexpanded state such that eachstent element lengthens and the space between the stent elements isreduced to 1 mm or less.

This and other aspects of the present disclosure are described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

Present embodiments have other advantages and features which will bemore readily apparent from the following detailed description and theappended claims, when taken in conjunction with the accompanyingdrawings, in which:

FIG. 1 shows the typical radial resistive forces of intravascularstents.

FIG. 2A illustrates one embodiment of a multi-element stent. FIG. 2B isa magnified view of the stent elements in FIG. 2A.

FIGS. 3A-3C depict deployment of a balloon-expandable multi-elementstent.

FIG. 4A shows an implanted multi-element stent in a popliteal arteryduring full flexion of the hip and knee. FIG. 4B depicts the implanteddevice of FIG. 4A shown in three dimensions.

FIGS. 5A-5C are side views of a self-expanding Nitinol stent placed in adistal SFA and popliteal artery, illustrated during different amounts ofleg flexion.

FIG. 6 depicts an angle created between stent elements during maximalflexion of the target vessel location during skeletal movement.

FIGS. 7A-7D show an embodiment of a stent pattern. FIG. 7A is atwo-dimensional depiction of an element. FIG. 7B shows a magnified viewof the cells in FIG. 7A. FIGS. 7C and 7D show the stent element of FIG.7A in cylindrical form.

FIGS. 8A-8D show cell views of patterns of stent elements that shortenupon expansion.

FIG. 9 shows a laser cut stent.

FIGS. 10A-10E show a multi-element stent mounted on an angioplastyballoon.

FIGS. 11A-11F show finite element analysis (FEA) of a bioresorbablepolymer stent cell that lengthens upon crimping and shortens uponexpansion.

FIGS. 12A-12D show cell patterns with various connector configurations.

FIGS. 13A-13C show a two-segment device deployed in the left iliofemoralartery.

FIG. 14 shows an optical coherence tomographic (OCT) image of a deployedbioresorbable stent in the porcine iliofemoral artery.

FIGS. 15A-C show Micro-CT images of a scaffolded artery.

FIGS. 16A and 16B show eight serial balloon-expandable stent segmentsimplanted the full length of a porcine iliofemoral artery.

FIG. 17 is a schematic diagram of a micro-stereolithograph used tocreate a stent, according to one embodiment.

DETAILED DESCRIPTION

While the invention has been disclosed with reference to certainembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted withoutdeparting from the scope of the invention. In addition, manymodifications may be made to adapt to a particular situation or materialto the teachings of the invention without departing from its scope.

Throughout the specification and claims, the following terms take themeanings explicitly associated herein unless the context clearlydictates otherwise. The meaning of “a”, “an”, and “the” include pluralreferences. The meaning of “in” includes “in” and “on.” Referring to thedrawings, like numbers indicate like parts throughout the views.Additionally, a reference to the singular includes a reference to theplural unless otherwise stated or inconsistent with the disclosureherein.

The word “exemplary” is used herein to mean “serving as an example,instance, or illustration.” Any implementation described herein as“exemplary” is not necessarily to be construed as advantageous overother implementations.

Various embodiments are described herein with reference to the figures.The figures are not drawn to scale and are only intended to facilitatethe description of the embodiments. They are not intended as anexhaustive description of the invention or as a limitation on the scopeof the invention. In addition, an illustrated embodiment needs not haveall the aspects or advantages shown. An aspect or an advantage describedin conjunction with a particular embodiment is not necessarily limitedto that embodiment and can be practiced in any other embodiments even ifnot so illustrated.

FIG. 1 shows the typical radial resistive forces of intravascularstents. A typical “bioresorbable vascular scaffold” (BVS) or absorbablestent has a radial resistive force of under 2 N/cm. Similarly, a typicalself-expanding metal stent (SES) has a radial resistive force of under 2N/cm. Typical balloon-expandable metal stents (BES) have a much higherradial resistive force, sometimes above 18 N/cm.

The embodiments herein describe the design of a new, intravascularabsorbable device that maintains the flow channel (patency) of longblood vessels by providing temporary, rigid, radial support that is fargreater than that provided by a typical absorbable or metalself-expanding stent (SES) and commensurate with that provided by ametal balloon-expandable stent (BES). Once implanted, the absorbabledevice imparts a high degree of radial force to prop open the diseasedartery; the force is roughly equivalent to a large diameter, peripheral,balloon-expandable metal stent.

In contrast to most stent patterns which are designed to marry bothradial force and longitudinal flexibility, the patterns described hereinare specifically tailored to maximize radial force and rigidity andforego longitudinal and axial flexibility.

The devices described herein are multi-element, vascular stents (or“vascular scaffolds”). These stents are comprised of multiple, short,rigid, cylindrical stent segments, or elements, which are separate fromone another but may be referred to together as a multi-element stent.

Generally, at least two of the elements of the multi-element stentdescribed herein will be sufficiently rigid to provide a desired levelof strength to withstand the stresses of the vessel in which they areplaced, such as a tortuous peripheral vessel. At the same time, a multielement stent will also be flexible, due to the fact that it is made upof multiple separate elements, thus allowing for placement within acurved, torturous blood vessel. In some embodiments, at least two of theelements vary in rigidity or radial strength in a multi-element stent.In one embodiment, the outer elements may have a lesser radial strengththan the inner elements in a multi-element stent. In another embodiment,a multi-element stent comprises elements having an increasing radialstrength serially along the length of the multi-element stent, such asin an AV fistula. Thus, the radial strength of elements may vary and betailored by known characteristics of a target artery.

Additionally, the multi element stents described herein will usually beballoon-expandable rather than self-expanding, since balloon-expandablestents are typically stronger than self-expanding stents. Each balloonexpandable element of the stent may have relatively high radial force(rigidity) due to the described structures and materials. A stentelement is defined as being radially rigid if it has a radial strengthsignificantly higher than self-expanding stents that is similar orgreater in magnitude to that of traditional, metal balloon-expandablestents, such as those made of steel or cobalt-chromium.

When mounted serially on an inflatable balloon, they can besimultaneously implanted side-by-side in long blood vessels. Duringmotion of the organism, the elements can move independently, maintainingtheir individual shape and strength while the intervening, non-stentedelements of the vessel can twist, bend and rotate unencumbered. Theresult is a treated vessel with a rigidly maintained flow channel thatstill enjoys unrestricted flexibility during organismal movement.

The described embodiments exploit the principles that, (1) a rigiddevice that is deployed via balloon-expansion represents the optimaldesign of an intravascular stent given its transient effect on thearterial wall and relative ease of precise implantation, (2) a long,rigid device cannot be safely implanted in an artery that bends andtwists with skeletal motion, (3) long arteries that bend and twist couldbe effectively treated with multiple, short BES that allow theintervening, non-stented arterial elements to move unencumbered, (4) thelength, number and spacing of the stent elements could be determined bythe known and predictable bending characteristics of the targetarteries, and (5) arteries need only be scaffolded transiently; latedissolution of the stent will have little effect on the long-termeffectiveness of treatment.

One embodiment of the fully assembled device in shown in FIG. 2A. Asingle balloon inflation and device deployment can treat a long segmentof diseased artery while still preserving the critical ability of theartery to bend with skeletal motion such as sitting or walking.Multi-element stent 200 comprises multiple stent elements 201.Individual balloon-expandable stent elements 201 are crimped onto aninflatable balloon 203 to facilitate delivery. FIG. 2B is a magnifiedview of the stent elements 201 in FIG. 2A. Individual elements 201 arepositioned serially along a longitudinal length of the balloon 203 andspaced such that the stent elements 201 do not touch one another.Further, the spacing is such that after deployment, the stent elements201 do not touch or overlap during skeletal movement. The number ofelements 201, length of elements, and gap 202 between elements 201 mayvary depending on the target vessel location. In an embodiment, eachelement 201 in the multi-element stent 200 has the same length. Inmulti-element stents having three or more elements 201, and thus two ormore gaps 202, the gaps may be of the same length.

FIGS. 3A-3C depict deployment of a balloon-expandable multi-elementstent. In FIG. 3A a multi-element stent mounted on a balloon is advancedto the lesion. In FIG. 3B the balloon and stent are expanded. In FIG. 3Cthe balloon is withdrawn leaving the multi-element stent still withinthe artery.

FIG. 4A shows an implanted multi-element stent in a popliteal arteryduring full flexion of the hip and knee. FIG. 4B depicts the implanteddevice of FIG. 4A shown in three dimensions. The individual stentelements 401 are spaced such that they do not overlap even when theartery is highly bent. Unencumbered arterial movement is affordedthrough flexion or extension of the unstented gaps 402.

Proper stent element length and the spacing between stent elements isimportant given the length and persistent motion of the extremityarteries. If stent elements are too long, the stent will lack sufficientlongitudinal flexibility. If the elements are placed too close together,they may overlap during movement leading to a similar lack of sufficientlongitudinal flexibility. This may lead to fracture of the stentelements. Fracture of intravascular stents is clearly associated withrestenosis. Likewise, if elements are too short or spaced too far apart,the lesion may not be sufficiently contact the target lesion. Properlength and spacing of the elements may be determined by the knowncharacteristics of the target artery.

FIGS. 5A-5C are side views of a self-expanding, Nitinol stent 500 placedin a distal SFA and popliteal artery, illustrated during differentamounts of leg flexion. FIG. 5A illustrates stent 500 with the leg inthe neutral position, minimal flexion/mostly extended. FIG. 5Billustrates stent 500 during partial flexion (70°/20° knee/hip flexion),with a circle and bend radius 502 illustrating the angle of flexion andthe curved deformation of stent 600. FIG. 5C illustrates stent 500during greater flexion (90°/90° knee/hip flexion). As FIGS. 5A-5Cillustrate, stent 500 is markedly deformed by movement of the leg. Thedrawn circle illustrates the use of bend radius 502 to describe thedegree of deformation. Stents that bend around a small circle (with asmall radius 502) are more deformed, e.g., the more deformed stent inthe FIG. 5C has a smaller bend radius 502 than the less deformed stent500 in FIG. 5B. The nearly straight stent in 5A has a very large bendradius that is too large to be accurately estimated.

Stent deformation after implantation in the femoropopliteal arteries isshown in Table 1. Perfect straightness is assigned a value of 180°.Deflection)(° is calculated as the difference between bend angles duringvarious degrees of extremity flexion. Note the significant bending ofpopliteal stents as compared to SFA stents.

TABLE 1 Stent deformation after implantation in the femoropoplitealarteries. SFA/prox SFA/prox SFA pop popliteal SFA pop popliteal N 11 2 611 2 6 Measured bend angle (°) Deflection (°) neutral position 169 ± 6 155 ± 11 167 ± 7  70°/20° knee/hip flexion 168 ± 3 146 ± 3 137 ± 18 4 ±3 9 ± 8 29 ± 12* 90°/90° knee/hip flexion 165 ± 5 148 ± 8 103 ± 21 5 ± 28 ± 4 64 ± 16* Measured bend radius (mm) 70°/20° knee/hip flexion NA NA 93 ± 52 90°/90° knee/hip flexion   135 ± 54** NA 22 ± 2 Sample sizesrefer to the number of treated lesions. Data are presented as mean ± SD.NA—not applicable (stent bending deformations are minimal and bendingradii are too large to be accurately measured). *p < 0.05 as compared toSFA or SFA/prox pop. **Stent bending radii measurable in 7 cases.

The length and spacing of the individual elements is partiallydetermined by the planned anatomic location of the device. For instance,available anatomic and physiologic data suggest that the superficialfemoral artery (SFA) is only minimally bent and compressed duringflexion of the thigh and knee (bending ˜7° and compression ˜5%) soindividual stent elements in the device intended for the SFA cantherefore be fairly closely spaced; they won't overlap even when the legis bent. In contrast, the popliteal artery more severely deforms whenthe hip and knee are flexed (bending ˜60° and compression ˜8%).Therefore, individual stent elements in the device intended for thepopliteal artery must be more widely spaced so they won't overlap duringskeletal movement.

FIG. 6 depicts an angle θ (25.609° as an example in an embodiment shownin FIG. 6 ) created between stent elements 601 during maximal flexion ofthe target vessel location during skeletal movement. Angle θ is acalculated angle governed by the maximum bend radius and the maximumindividual stent element 601 length for each anatomical location. Forthe SFA, angle θ is calculated to be 8.473°. For the popliteal, angle θis calculated to be 25.609°.

In an embodiment, the minimum necessary gap between elements can becalculated using the planned stent diameter (D) in the expanded state atthe target vessel location and the angle created between stent elementsduring maximal flexion of the vessel (0) at the target vessel location.The gap (G) may be calculated using the formula:

$G = \sqrt{\frac{D^{2}}{2}\left( {1 - {\cos\theta}} \right)}$

As can be seen from the given formula, if all other factors remain thesame, the distance between each stent element increases with anincreased diameter of the stent element. Similarly, if all other factorsremain the same, the distance between each stent element will be largerin the popliteal than the SFA. Table 2 shows calculated gaps using thisformula.

TABLE 2 Calculated element spacing taking into account planned stentdiameter and the angle created between stent elements during maximalflexion of the vessel Maximal Intended Maximal Bend Element ElementAnatomic Deflection Radius Length Diameter Length Number of SpacingLocation (°) (mm) (cm) (mm) (mm) Elements (mm) SFA 8 135 30 5.0 15 20.37 SFA 8 135 30 6.0 15 2 0.44 SFA 8 135 40 5.0 20 2 0.37 SFA 8 135 406.0 20 2 0.44 SFA 8 135 60 5.0 20 3 0.37 SFA 8 135 60 6.0 20 3 0.44 SFA8 135 80 5.0 20 4 0.37 SFA 8 135 80 6.0 20 4 0.44 SFA 8 135 80 8.0 20 40.59 SFA 8 135 100 3.0 20 5 0.22 SFA 8 135 100 4.0 20 5 0.30 SFA 8 135100 5.0 20 5 0.37 SFA 8 135 100 6.0 20 5 0.44 SFA 8 135 100 8.0 20 50.59 Popliteal 64 22 20 4.0 10 2 0.89 Popliteal 64 22 20 5.0 10 2 1.11Popliteal 64 22 30 4.0 10 3 0.89 Popliteal 64 22 30 5.0 10 3 1.11Popliteal 64 22 40 4.0 10 4 0.89 Popliteal 64 22 40 5.0 10 4 1.11Popliteal 64 22 60 4.0 10 6 0.89 Popliteal 64 22 60 5.0 10 6 1.11Popliteal 64 22 80 4.0 10 8 0.89 Popliteal 64 22 80 5.0 10 8 1.11Popliteal 64 22 100 3.0 10 10 0.66 Popliteal 64 22 100 4.0 10 10 0.89Popliteal 64 22 100 5.0 10 10 1.11 Popliteal 64 22 100 6.0 10 10 1.33Popliteal 64 22 100 8.0 10 10 1.77

Ideal gap length between stent elements may also be influenced by axialstent compression or shortening during extremity flexion. Table 3 showsaxial stent compression after implantation in the femoropoplitealarteries. The amount of axial compression is calculated as thedifference between measured stent lengths during various degrees ofextremity flexion.

TABLE 3 Axial stent compression after implantation in thefemoropopliteal arteries Measured stent length (mm) Axial compression(%) SFA/prox SFA/prox SFA pop popliteal SFA pop popliteal Single 80 mmstents N 6 1 1 6 1 1 neutral position 80 ± 2  73 79  70°/20° knee/hipflexion 78 ± 2  72 76  2.0 ± 1.8 2.7 3.1 90°/90° knee/hip flexion 77 ±2  70 71  3.5 ± 2.1 5.0 9.3 Single 100 mm stents N 4 1 3 4 1 3 neutralposition 101 ± 2  94 100 ± 3  70°/20° knee/hip flexion 99 ± 3  92 98 ± 11.4 ± 1.9 2.1 2.0 ± 1.7 90°/90° knee/hip flexion 98 ± 1  88 92 ± 6 2.9 ±1.4 5.7 8.4 ± 5.0 Overlapped stents N 1 2 1 2 neutral position 96.6 118± 75 70°/20° knee/hip flexion 96.5 112 ± 74 0.1 6.1 ± 3.0 90°/90°knee/hip flexion 89.8 108 ± 70 7.0 8.4 ± 1.6 All stents (includingoverlapped) N 11 2 6 11 2 6 neutral position 91 ± 14 84 ± 14 102 ± 3670°/20° knee/hip flexion 90 ± 15 82 ± 14  99 ± 35 1.7 ± 1.7 2.4 ± 0.43.5 ± 2.7 90°/90° knee/hip flexion 88 ± 15 79 ± 13  94 ± 35 3.1 ± 1.85.3 ± 0.5  8.5 ± 3.2* Sample sizes refer to the number of treatedlesions. Data are presented as mean ± SD. *p < 0.05 as compared to SFA.

Ideal gap length taking into account axial compression may be calculatedusing the formula:

Gap=((LEC+GEC-GC)/(e−1))+G

L is the stent element length. E is the number of stent elements. G isthe gap length calculated using the previous formula. C is the maximumpercent axial compression for the target vessel location. For the SFA, Cis approximately 5%. For the popliteal, C is approximately 8%.

As can be seen from this formula, if all other factors remain the same,the distance between each stent element increases with an increase inlength of the stent elements. Likewise, if all other factors remain thesame, the distance between each stent element decreases with an increasein the number of elements in the multi-element stent. Similarly, if allother factors remain the same, the distance between each stent elementincreases with an increase of the maximum percent axial compression ofthe stent elements at the target vessel location. The approximaterelationship between device diameter, length, number of elements andelement spacing for devices intended for the superficial femoral arteryare shown in Table 4. The approximate relationship between devicediameter, length, number of elements and element spacing for devicesintended for the popliteal artery are shown in Table 5.

TABLE 4 The approximate relationship between device diameter, length,number of elements and element spacing for devices intended for thesuperficial femoral artery Maximal Maximal Maximal bend axial ElementNumber Element Deflection radius compression Length Diameter Length ofSpacing (°) (mm) (%) (mm) (mm) (mm) Elements (mm) 8 135 5 20 3.0 10 21.23 8 135 5 20 4.0 10 2 1.31 8 135 5 20 5.0 10 2 1.39 8 135 5 20 6.0 102 1.47 8 135 5 20 8.0 10 2 1.62 8 135 5 30 3.0 15 2 1.73 8 135 5 30 4.015 2 1.81 8 135 5 30 5.0 15 2 1.89 8 135 5 30 6.0 15 2 1.97 8 135 5 308.0 15 2 2.12 8 135 5 40 3.0 20 2 2.23 8 135 5 40 4.0 20 2 2.31 8 135 540 5.0 20 2 2.39 8 135 5 40 6.0 20 2 2.47 8 135 5 40 8.0 20 2 2.62 8 1355 60 3.0 20 3 1.73 8 135 5 60 4.0 20 3 1.81 8 135 5 60 5.0 20 3 1.89 8135 5 60 6.0 20 3 1.97 8 135 5 60 8.0 20 3 2.12 8 135 5 80 3.0 20 4 1.578 135 5 80 4.0 20 4 1.64 8 135 5 80 5.0 20 4 1.72 8 135 5 80 6.0 20 41.80 8 135 5 80 8.0 20 4 1.95 8 135 5 100 3.0 20 5 1.48 8 135 5 100 4.020 5 1.56 8 135 5 100 5.0 20 5 1.64 8 135 5 100 6.0 20 5 1.72 8 135 5100 8.0 20 5 1.87

TABLE 5 The approximate relationship between device diameter, length,number of elements and element spacing for devices intended for thepopliteal artery Maximal Maximal Maximal bend axial Element NumberElement Deflection radius compression Length Diameter Length of Spacing(°) (mm) (%) (mm) (mm) (mm) Elements (mm) 64 22 8 20 3.0 10 2 2.32 64 228 20 4.0 10 2 2.56 64 22 8 20 5.0 10 2 2.80 64 22 8 20 6.0 10 2 3.04 6422 8 20 8.0 10 2 3.51 64 22 8 30 3.0 10 3 1.92 64 22 8 30 4.0 10 3 2.1664 22 8 30 5.0 10 3 2.40 64 22 8 30 6.0 10 3 2.64 64 22 8 30 8.0 10 33.11 64 22 8 40 3.0 10 4 1.78 64 22 8 40 4.0 10 4 2.02 64 22 8 40 5.0 104 2.26 64 22 8 40 6.0 10 4 2.50 64 22 8 40 8.0 10 4 2.98 64 22 8 60 3.010 6 1.68 64 22 8 60 4.0 10 6 1.92 64 22 8 60 5.0 10 6 2.16 64 22 8 606.0 10 6 2.40 64 22 8 60 8.0 10 6 2.87 64 22 8 80 3.0 10 8 1.63 64 22 880 4.0 10 8 1.87 64 22 8 80 5.0 10 8 2.11 64 22 8 80 6.0 10 8 2.35 64 228 80 8.0 10 8 2.83 64 22 8 100 3.0 10 10 1.61 64 22 8 100 4.0 10 10 1.8564 22 8 100 5.0 10 10 2.09 64 22 8 100 6.0 10 10 2.33 64 22 8 100 8.0 1010 2.80

The stents described herein may be formed from various differentmaterials. In an embodiment, stents may be formed a polymer. In variousalternative embodiments, the stent or stent element may be made from anysuitable bioresorbable material such that it will dissolve non-toxicallyin the human body, such as but not limited to poly(L-lactic acid)(PLLA), polyglycolic acid (PGA), poly(iodinated desaminotyrosyl-tyrosineethyl ester) carbonate, or the like. In one embodiment, at least two ofthe elements comprise different materials. For example, the outerelements may comprise of a faster degrading bioresorbable material thanthe inner elements of a bioresorbable, multi-element stent.

In alternative embodiments, any suitable polymer may be used toconstruct the stent. The term “polymer” is intended to include a productof a polymerization reaction inclusive of homopolymers, copolymers,terpolymers, etc., whether natural or synthetic, including random,alternating, block, graft, branched, cross-linked, blends, compositionsof blends and variations thereof. The polymer may be in true solution,saturated, or suspended as particles or supersaturated in the beneficialagent. The polymer can be biocompatible, or biodegradable. For purposeof illustration and not limitation, the polymeric material may include,but is not limited to, poly(D-lactic acid) (PDLA), poly(D,L-lactic acid)(PDLLA), poly(iodinated desamino tyrosyl-tyrosine ethyl ester)carbonate, poly(lactic-co-glycolic acid) (PLGA), salicylate basedpolymer, semicrystalline polylactide, phosphorylcholine,polycaprolactone (PCL), poly-D,L-lactic acid, poly-L-lactic acid,poly(lactideco-glycolide), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polydioxanone (PDS), polyorthoester,polyanhydride, poly(glycolic acid), poly(glycolic acid-co-trimethylenecarbonate), polyphosphoester, polyphosphoester urethane, poly(aminoacids), cyanoacrylates, poly(trimethylene carbonate),poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes,polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen,cellulose, starch, collagen, polyurethane including polycarbonateurethanes, polyethylene, polyethylene terephthalate, ethylene vinylacetate, ethylene vinyl alcohol, silicone including polysiloxanes andsubstituted polysiloxanes, polyethylene oxide, polybutyleneterephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL,polyacrylates, polyvinyl pyrrolidone, polyacrylamide, and combinationsthereof. Non-limiting examples of other suitable polymers includethermoplastic elastomers in general, polyolefin elastomers, EPDM rubbersand polyamide elastomers, and biostable plastic material includingacrylic polymers, and its derivatives, nylon, polyesters and expoxies.In some embodiments, the stent may include one or more coatings, withmaterials like poly(D,L-lactic acid) (PDLLA). These materials are merelyexamples, however, and should not be seen as limiting the scope of theinvention.

Stent elements may comprise various shapes and configurations. Some orall of the stent elements may comprise closed-cell structures formed byintersecting struts. Closed-cell structures may comprise diamond,square, rectangular, parallelogrammatic, triangular, pentagonal,hexagonal, heptagonal, octagonal, clover, lobular, circular, elliptical,and/or ovoid geometries. Closed-cells may also comprise slotted shapessuch as H-shaped slots, I-shaped slots, J-shaped slots, and the like.Additionally or alternatively, stent may comprise open cell structuressuch as spiral structures, serpentine structures, zigzags structures,etc. Strut intersections may form pointed, perpendicular, rounded,bullnosed, flat, beveled, and/or chamfered cell corners. In anembodiment, stent may comprise multiple different cells having differentcell shapes, orientations, and/or sizes. Various cell structures havebeen described in PCT International Application Number PCT/US16/20743,entitled “MULTI-ELEMENT BIORESORBABLE INTRAVASCULAR STENT”, the fulldisclosure of which is herein incorporated by reference.

Returning to FIG. 2B, in this exemplary embodiment, the stent elements201 have a diamond shaped closed-cell pattern. Elements 201 compriseintermixed diamond shaped closed cells 204, 205. Diamond shaped cells204 may be aligned in the longitudinal and/or the circumferentialdirections in a repeating pattern. Similarly, diamond shaped cells 205may be aligned in the longitudinal and/or the circumferential directionsin a repeating pattern. Additionally or alternatively, diamond shapedcells 204 and diamond shaped cells 205 may be helically aligned in analternating pattern. In an embodiment, diamond shaped cells 204 anddiamond shaped cells 205 are circumferentially offset. Additionally,diamond shaped cells 205 may be formed at a central location betweenfour adjacent diamond shaped cells 204. The width of struts 206 betweentwo corners of longitudinally aligned diamond shaped cells 204 arelarger than the width of struts 207 between two corners oflongitudinally aligned diamond shaped cells 205.

In contrast to most balloon-expandable stent patterns which are designedto minimize foreshortening upon stent expansion, various patternsdescribed herein are specifically designed to shorten upon expansion,such that the length of deployed element is considerably less than thelength of the element when crimped. Heretofore felt to be an undesirableproperty of intravascular stents, the patterns described herein areactually intended to shorten to create the final result of discontinuityof the fully deployed device within the vessel.

One embodiment of a stent pattern designed to shorten upon expansion isshown in shown in FIGS. 7A-7D. The structure of a stent pattern may bedesigned for maximal radial force and stiffness which will lengthen whencrimped and foreshorten when expanded. The stent elements 701 have adiamond shaped closed-cell pattern with relatively thick strut widthsand obliquely-angled links. Elements 701 comprise diamond shaped closedcells 704. Elements 701 may comprise wide struts 706 of 225 microns orlarger. Elements 701 may similarly comprise thick struts 706 of 225microns or larger. In an embodiment, elements 701 comprise struts 706with a width and/or thickness of approximately 250 microns. The widthand/or the height of struts 706 between two corners of diamond shapedcells 704 may be larger or smaller than the width and/or height ofstruts 706 forming the sides of diamond shaped cells 704.

FIGS. 8A-8D show cell views of patterns of stent elements that shortenupon expansion. Individual cell patterns of absorbable intravascularstents designed for maximal radial force and stiffness which willlengthen when crimped and foreshorten when expanded. Stent elements mayhave diamond-shaped, closed cell structure with relatively thick strutwidths and obliquely-angled links.

An example of an actual laser-cut stent designed herein is shown in FIG.9 . FIGS. 10A-10E show two such segments mounted on a standardangioplasty balloon. FIG. 10A shows two segments crimped on anangioplasty balloon. The segments were applied with an intervening spacewhich was eliminated as the stents lengthened during crimping. To thenaked eye, the device appears as a single, continuous stent. However,when then balloon is inflated the two rigid stent segments shorten so asto create an intervening space between them (FIGS. 10B-10E). As thesegments are rigid, the intervening space allows for the artery to bendwith normal skeletal motion.

There are several parameters that may be manipulated to engineer thedesired spacing between elements. Examples of seven of these parametersare provided here.

Parameter 1: Stent Pattern

The stent pattern generally affects the amount of foreshortening a stentundergoes during expansion. The more a given pattern foreshortens, thelarger a space is created between the elements. Many features of thestent pattern can be manipulated to achieve the desired amount offoreshortening and inter-element spacing.

One feature that can be manipulated is the change of angle that thestruts undergo during expansion. The change of angle can be seen inFIGS. 11A-11F. FIGS. 11A-11F show finite element analysis (FEA) of abioresorbable polymer stent cell that lengthens upon crimping andshortens upon expansion. The stress scale is shown at the left. FIGS.11A-11F show progressive crimping of a single cell 1104. Note themaximal stress of 156 mises even when fully crimped (FIG. 11F)demonstrates that the device can be effectively crimped without unduestrain or fracture. In 11F, the struts are in the crimped configurationprior to expansion and each strut is essentially horizontal. In 11A, thestruts are in the fully expanded configuration and each strut hasrotated from a horizontal orientation to a more upright orientation. Thelarger this change of angle, the more the pattern will foreshorten inthe case of a closed cell pattern. Changing the length of struts or thenumber of cells circumferentially around the stent element can affectthe change in angle.

In the case of an open cell pattern, a larger change of angle of thestruts during expansion may increase, decrease, or not affectforeshortening depending on the configuration of the connectors betweenrings. FIGS. 12A-12D show cell patterns with various connectorconfigurations. If connectors 1201 connect the peaks 1202 of one ring tothe peaks 1202 of another ring (FIG. 12A), that portion of the patternwill react like a closed cell pattern and increased change of angle ofthe struts will cause increased foreshortening and increaseinter-element spacing. If the connectors 1201 connect the valleys 1203of one ring to the valleys 1203 of another (FIG. 12B), increased changeof the angle of the struts will cause lengthening upon expansion andthat portion of the pattern will cause decreased inter-element spacing.If the connectors 1201 connect the valleys 1203 of one ring to the peaks1202 of another (FIG. 12C), increased change of the angle of the strutswill not affect the length of the stent during expansion.

The various connector configurations mentioned above may be usedcombined with each other and/or with a closed cell pattern to manipulatethe amount of foreshortening and the size of the inter-element spacing.For example, the pattern shown in FIG. 12D combines one ring of opencell pattern with every two rings of a closed cell pattern. Theparticular connector 1201 configuration in the open cell portioncontributes lengthening upon expansion while the closed cell portionforeshortens upon expansion. The lengthening partially offsets theforeshortening thus leading to a smaller amount of foreshortening thanwhat would result from using only a closed cell pattern.

Parameter 2: Element Length:

Given a certain amount of foreshortening per unit length of a stentelement, the amount of foreshortening in absolute terms is proportionalto the length of the element. Since the inter-element spacing isdetermined by the amount of foreshortening, it is also proportional tothe element length.

Parameter 3: Deployment Diameter:

For a stent element that foreshortens during deployment and creates aspace to the next element, the foreshortening and the space created bothbecome larger as the diameter to which the element is expanded becomeslarger.

Parameter 4: Crimped Spacing:

The spacing between the elements after deployment may be directlymanipulated by changing the spacing before deployment when the elementsare crimped onto the balloon. In the example device shown in FIGS.10A-10F, the elements are crimped such that they are touching and all ofthe inter-element space is created by foreshortening and/or movement ofthe elements. However, this is not a requirement. The elements may alsobe crimped with pre-existing spacing that is increased duringdeployment. In an embodiment, elements may be crimped with apre-existing space of 1 mm or less.

Parameter 5: Stent Material:

The stent material may impact the amount of space created in two ways.First, because different materials can undergo differing amounts ofstrain before fracturing and different stent patterns cause the materialto undergo different amounts of strain during deployment, the materialused impacts the design of the stent pattern. Second, even when the samestent pattern is used, different materials may react differently to boththe crimping and deployment processes thus resulting is differentamounts of foreshortening and influencing the size of the inter-elementspaces.

Parameter 6: Crimping Process Variables:

Balloon expandable bioresorbable stents may be first manufactured at adiameter approximating the eventual deployment diameter and then crimpedor collapsed into a smaller diameter onto a balloon via a crimpingprocess. A stent element that foreshortens during deployment, lengthensduring the crimping process. The amount of lengthening and thedeformation of the stent pattern that occur during crimping can both beaffected by several variables of the crimping process. The amount oflengthening that a stent element undergoes during crimping, in turn,affects the amount that the element foreshortens during deployment andthe size of the inter-element spaces created. The variables that affectlengthening during the crimping process include the temperature at whichcrimping is performed, the time over which crimping takes place, thepresence or absence of an inflated balloon during portions of thecrimping process and the pressure of the balloon. For example, if ahigher temperature is used during crimping, the material may becomesofter and the struts of the stent may deform more during crimpingleading to a lower amount of lengthening which in turn would lead toless foreshortening during deployment.

Parameter 7: Balloon Material:

The material of the balloon used to deploy the stent can affect the sizeof the inter-elements spaces because different balloon materials producedifferent amounts of friction between the balloon and the stent. Thusdiffering balloon materials may allow more or less movement of the wholestent element or just portions of the element relative to the balloon.This can affect the size of the inter-element spaces in two ways. First,the movement allowed affects the amount of lengthening that occurs inthe elements during crimping and the amount of foreshortening thatoccurs during deployment. Second, the movement allowed may affectmovement of the entire element during deployment. For example, if aspace opens up between two elements during deployment, the elements mayslide away from each other increasing the size of the space. The amountthat the elements slide apart would be affected by the material of theballoon.

An embodiment of the device was tested acutely by implantation intoexperimental animals. Domestic farm pigs were anesthetized withketamine, azaperone and atropine administered intramuscularly. Viasurgical exposure, a sheath was placed in the right common carotidartery and wire access of the left iliofemoral arterial system securedunder fluoroscopic control. A two-segment device was deployed in theleft iliofemoral artery as shown in FIGS. 13A-13C. In FIG. 13A, the lefthind limb is extended. FIG. 13B shows the animal's hind limb flexed tosimulate flexion of the human superficial femoral artery. The arterybends in the intervening space between the two stents; the scaffoldsegments themselves remain rigid and straight. FIG. 13C shows extreme,non-physiologic flexion of the hind limb. The stented artery remainedpatent by bending within the intervening space between the two rigidstents

Following deployment, Optimal Coherence Tomographic (OCT) imaging wasperformed using the Illumien Optis imaging system (Abbott Laboratories,Abbott Park, Ill.). The OCT catheter was advanced beyond the device,into the distal vessel, and pulled back to a point proximal to thedevice. An optical coherence tomographic (OCT) image of the deployedbioresorbable stent in the porcine iliofemoral artery is shown in FIG.14 . Because of the high radial strength of the device, all scaffoldstruts are completely opposed to the arterial wall.

Following deployment and imaging, the animal was euthanized by a lethalinjection of saturated potassium chloride while maintaining deepanesthesia. The lower body was perfused with lactated Ringer's solutionthen neutral buffered formalin. The scaffolded artery was excised andtreated with graded alcohol then scanned using a Nikon XT H 225micro-computed tomograph. Micro-CT images are shown in FIGS. 15A-C. Thescaffolded artery is shown intact in FIG. 15A. Subtraction of theanterior arterial wall is shown in FIG. 15B. FIG. 15C shows subtractionof the entire arterial wall. The devices shortened upon expansioncreating an intervening space about which the supple artery has hinged.

Eight serial balloon-expandable stent segments were implanted the fulllength of the porcine iliofemoral artery. The results are shown in FIGS.16A and 16B. A total of eight segments were implanted in approximately12 cm of total iliofemoral arterial length. FIG. 16A shows the animal'shind limb extended. Aortic injection demonstrates wide patency of thestented artery. Patency is redemonstrated even when the hind limb ismanually flexed (FIG. 16B). Even though the artery has been treated withmultiple, serial, rigid stents, its capacity for motion is preserved bythe intervening spaces created by stent shortening.

The device described herein may include incorporation of a therapeuticdrug on one or more of the stent elements of the multi-element stent. Inone embodiment, the therapeutic drug may be intended to prevent orattenuate pathologic consequences of intraluminal intervention such asinflammation, cell dysfunction, cell activation, cell proliferation,neointimal formation, thickening, late atherosclerotic change and/orthrombosis. Any suitable therapeutic agent (or “drug”) may beincorporated into, coated on, or otherwise attached to the stent, invarious embodiments. Examples of such therapeutic agents include, butare not limited to, antithrombotics, anticoagulants, antiplateletagents, anti-lipid agents, thrombolytics, antiproliferatives,anti-inflammatories, agents that inhibit hyperplasia, smooth muscle cellinhibitors, antibiotics, growth factor inhibitors, cell adhesioninhibitors, cell adhesion promoters, antimitotics, antifibrins,antioxidants, anti-neoplastics, agents that promote endothelial cellrecovery, matrix metalloproteinase inhibitors, anti-metabolites,antiallergic substances, viral vectors, nucleic acids, monoclonalantibodies, inhibitors of tyrosine kinase, antisense compounds,oligonucleotides, cell permeation enhancers, hypoglycemic agents,hypolipidemic agents, proteins, nucleic acids, agents useful forerythropoiesis stimulation, angiogenesis agents, anti-ulcer/anti-refluxagents, and anti-nauseants/anti-emetics, PPAR alpha agonists such asfenofibrate, PPAR-gamma agonists selected such as rosiglitazaone andpioglitazone, sodium heparin, LMW heparins, heparoids, hirudin,argatroban, forskolin, vapriprost, prostacyclin and prostacylinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticanti-thrombin), glycoprotein IIb/IIIa (platelet membrane receptorantagonist antibody), recombinant hirudin, thrombin inhibitors,indomethacin, phenyl salicylate, beta-estradiol, vinblastine, ABT-627(astrasentan), testosterone, progesterone, paclitaxel, methotrexate,fotemusine, RPR-101511A, cyclosporine A, vincristine, carvediol,vindesine, dipyridamole, methotrexate, folic acid, thrombospondinmimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol,iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol,and iotrolan, antisense compounds, inhibitors of smooth muscle cellproliferation, lipid-lowering agents, radiopaque agents,antineoplastics, HMG CoA reductase inhibitors such as lovastatin,atorvastatin, simvastatin, pravastatin, cerivastatin and fluvastatin,and combinations thereof.

Examples of antithrombotics, anticoagulants, antiplatelet agents, andthrombolytics include, but are not limited to, sodium heparin,unfractionated heparin, low molecular weight heparins, such asdalteparin, enoxaparin, nadroparin, reviparin, ardoparin and certaparin,heparinoids, hirudin, argatroban, forskolin, vapriprost, prostacyclinand prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone(synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa (plateletmembrane receptor antagonist antibody), recombinant hirudin, andthrombin inhibitors such as bivalirudin, thrombin inhibitors, andthrombolytic agents, such as urokinase, recombinant urokinase,pro-urokinase, tissue plasminogen activator, ateplase and tenecteplase.

Examples of cytostatic or antiproliferative agents include, but are notlimited to, rapamycin and its analogs, including everolimus,zotarolimus, tacrolimus, novolimus, and pimecrolimus, angiopeptin,angiotensin converting enzyme inhibitors, such as captopril, cilazaprilor lisinopril, calcium channel blockers, such as nifedipine, amlodipine,cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem andverapamil, fibroblast growth factor antagonists, fish oil (omega 3-fattyacid), histamine antagonists, lovastatin, topoisomerase inhibitors, suchas etoposide and topotecan, as well as antiestrogens such as tamoxifen.

Examples of anti-inflammatory agents include, but are not limited to,colchicine and glucocorticoids, such as betamethasone, cortisone,dexamethasone, budesonide, prednisolone, methylprednisolone andhydrocortisone. Non-steroidal anti-inflammatory agents include, but arenot limited to, flurbiprofen, ibuprofen, ketoprofen, fenoprofen,naproxen, diclofenac, diflunisal, acetominophen, indomethacin, sulindac,etodolac, diclofenac, ketorolac, meclofenamic acid, piroxicam andphenylbutazone.

Examples of antineoplastic agents include, but are not limited to,alkylating agents including altretamine, bendamucine, carboplatin,carmustine, cisplatin, cyclophosphamide, fotemustine, ifosfamide,lomustine, nimustine, prednimustine, and treosulfin, antimitotics,including vincristine, vinblastine, paclitaxel, docetaxel,antimetabolites including methotrexate, mercaptopurine, pentostatin,trimetrexate, gemcitabine, azathioprine, and fluorouracil, antibiotics,such as doxorubicin hydrochloride and mitomycin, and agents that promoteendothelial cell recovery such as estradiol.

Antiallergic agents include, but are not limited to, permirolastpotassium nitroprusside, phosphodiesterase inhibitors, prostaglandininhibitors, suramin, serotonin blockers, steroids, thioproteaseinhibitors, triazolopyrimidine, and nitric oxide.

The beneficial agent may include a solvent. The solvent may be anysingle solvent or a combination of solvents. For purpose of illustrationand not limitation, examples of suitable solvents include water,aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ketones,dimethyl sulfoxide, tetrahydrofuran, dihydrofuran, dimethylacetamide,acetates, and combinations thereof.

Stents may be manufactured using an additive or a subtractive. In any ofthe described embodiments, stents or stent elements may be manufacturedas a sheet and wrapped into cylindrical form. Alternatively, stents orstent elements may be manufactured in cylindrical form using an additivemanufacturing process. In an embodiment, stents may be formed byextruding a material into a cylindrical tubing. In some embodiments, alonger stent element, may be formed during the manufacturing process andthen cut into smaller stent elements/elements to provide a multi-elementstent. In an embodiment, stent tubing may be laser cut with a pattern toform a stent element.

Referring now to FIG. 17 , in one embodiment, stents may be manufacturedusing a micro-stereolithography system 100 (or “3D printing system”).Several examples of currently available systems that might be used invarious embodiments include, but are not limited to: MakiBox A6, MakibleLimited, Hong Kong; CubeX, 3D Systems, Inc., Circle Rock Hill, S.C.; and3D-Bioplotter, (EnvisionTEC GmbH, Gladbeck, Germany).

The micro-stereolithography system may include an illuminator, a dynamicpattern generator, an image-former and a Z-stage. The illuminator mayinclude a light source, a filter, an electric shutter, a collimatinglens and a reflecting mirror that projects a uniformly intense light ona digital mirror device (DMD), which generates a dynamic mask. FIG. 10shows some of these components of one embodiment of themicro-stereolithography system 100, including a DMD board, Z-stage,lamp, platform, resin vat and an objective lens. The details of 3Dprinting/micro-stereolithography systems and other additivemanufacturing systems will not be described here, since they are wellknown in the art. However, according to various embodiments, anyadditive manufacturing system or process, whether currently known orhereafter developed, may potentially be used to fabricate stents withinthe scope of the present invention. In other words, the scope of theinvention is not limited to any particular additive manufacturing systemor process.

In one embodiment, the system 100 may be configured to fabricate stentsusing dynamic mask projection micro-stereolithography. In oneembodiment, the fabrication method may include first producing 3Dmicrostructural scaffolds by slicing a 3D model with a computer programand solidifying and stacking images layer by layer in the system. In oneembodiment, the reflecting mirror of the system is used to project auniformly intense light on the DMD, which generates a dynamic mask. Thedynamic pattern generator creates an image of the sliced section of thefabrication model by producing a black-and-white region similar to themask. Finally, to stack the images, a resolution Z-stage moves up anddown to refresh the resin surface for the next curing. The Z-stage buildsubsystem, in one embodiment, has a resolution of about 100 nm andincludes a platform for attaching a substrate, a vat for containing thepolymer liquid solution, and a hot plate for controlling the temperatureof the solution. The Z-stage makes a new solution surface with thedesired layer thickness by moving downward deeply, moving upward to thepredetermined position, and then waiting for a certain time for thesolution to be evenly distributed.

Although particular embodiments have been shown and described, they arenot intended to limit the invention. Various changes and modificationsmay be made to any of the embodiments, without departing from the spiritand scope of the invention. The invention is intended to coveralternatives, modifications, and equivalents.

What is claimed is:
 1. A device for placement within a blood vessel tomaintain or enhance blood flow through the blood vessel, the devicecomprising: multiple, balloon-expandable, bioresorbable, vascular stentelements configured to be implanted in the blood vessel as amulti-element stent; wherein the stent elements are positioned seriallyalong a longitudinal length of a balloon with a space between the stentelements in an unexpanded state of 0.44 mm or less; wherein the stentelements are configured to shorten upon balloon expansion to an expandedstate at a target vessel location to increase the space between thestent elements in the expanded state such that the stent elements do nottouch one another at the target vessel location during skeletalmovement; and wherein the stent is configured to be radially rigid andlongitudinally flexible after implantation at the target vessellocation.
 2. The device of claim 1, wherein a cell pattern of the stentelements is configured to shorten the stent elements upon expansion andprovide the space between the stent elements in the expanded state. 3.The device of claim 2, wherein the stent elements comprise one or moreshortening sections configured to shorten upon expansion to the expandedstate.
 4. The device of claim 3, wherein the shortening sectioncomprises closed cells.
 5. The device of claim 3, wherein the shorteningsection comprises open cells with one or more struts connecting one ormore peaks of a first ring to one or more peaks of a second ring.
 6. Thedevice of claim 1, wherein the stent elements are positioned seriallyalong a longitudinal length of a balloon with a space between the stentelements in an unexpanded state of 0.22 mm or less.
 7. The device ofclaim 1, wherein at least two of the stent elements have differentdiameters.
 8. The device of claim 1, wherein the stent elements aretouching while positioned serially along the longitudinal length of theballoon in the unexpanded state.
 9. The device of claim 1, wherein theradial rigidity of the device is slowly attenuated as its structuralpolymer is unlinked and metabolized such that the device slowly becomesmore flexible causing adaptation and remodeling of the vessel andrestoration of the vessel's elasticity.
 10. A method for manufacturingan intravascular stent comprising: loading a multi-element stentcomprising multiple individual stent elements onto an inflatable balloonin an expanded state such that the stent elements are positionedserially along a longitudinal length of the balloon and the stentelements do not touch one another, wherein the stent elements are spacedsuch that the stent elements do not touch one another at a target vessellocation during skeletal movement; and deflating the balloon andcrimping the multi-element stent to an unexpanded state such that eachstent element lengthens and the space between the stent elements isreduced to 0.44 mm or less.
 11. The method of claim 10, wherein theballoon is deflated and the multi-element stent is crimped to theunexpanded state such that the stent elements are touching.
 12. A devicefor placement within a blood vessel to maintain or enhance blood flowthrough the blood vessel, the device comprising: multiple,balloon-expandable, bioresorbable, vascular stent elements configured tobe implanted in the blood vessel as a multi-element stent; wherein atleast two of the stent elements are positioned serially along alongitudinal length of a balloon with a space between the stent elementsin an unexpanded state of 0.44 mm or less; wherein the at least twostent elements are configured to shorten upon balloon expansion to anexpanded state at a target vessel location to increase the space betweenthe stent elements in the expanded state such that the stent elements donot touch one another at the target vessel location during skeletalmovement; and wherein the at least two stent elements are configured tohave a radial resistive force of 18 N/cm or more after implantation atthe target vessel location.
 13. The device of claim 12, wherein the atleast two stent elements are positioned serially along a longitudinallength of a balloon with a space between the stent elements in anunexpanded state of 0.22 mm or less.
 14. The device of claim 13, whereina cell pattern of the at least two stent elements is configured toshorten the stent elements upon expansion and provide the space betweenthe stent elements in the expanded state.
 15. The device of claim 14,wherein the at least two stent elements comprise one or more shorteningsections configured to shorten upon expansion to the expanded state. 16.The device of claim 15, wherein the shortening section comprises closedcells.
 17. The device of claim 15, wherein the shortening sectioncomprises open cells with one or more struts connecting one or morepeaks of a first ring to one or more peaks of a second ring.
 18. Thedevice of claim 12, wherein the at least two stent elements are touchingwhile positioned serially along the longitudinal length of the balloon.19. The device of claim 12, wherein the at least two stent elements areformed from different bioresorbable polymer material.
 20. The device ofclaim 12, wherein the at least two elements have different diameters.